Neuropsychopharmacology,
Journal Year:
2024,
Volume and Issue:
49(12), P. 1916 - 1924
Published: July 1, 2024
Prevailing
hypotheses
on
the
mechanisms
of
antidepressant
action
posit
that
antidepressants
directly
counteract
deficiencies
in
major
neurotransmitter
signaling
systems
underlie
depression.
The
rapidly
acting
ketamine
has
been
postulated
to
correct
excess
glutamatergic
via
antagonism
leading
rescue
neuronal
structural
deficits
and
reversal
behavioral
symptoms.
We
studied
this
premise
using
systemic
administration
acetylcholinesterase
inhibitor
physostigmine,
which
shown
elicit
a
shorter-term
period
depressed
mood
humans
cholinergic
mechanisms.
observed
physostigmine
induces
acute
stress
tandem
with
long
term
depression
glutamate
release
hippocampus
mice.
However,
acts
re-establish
synaptic
efficacy
postsynaptic
behaviorally
masks
reduction
passive
coping
induced
by
physostigmine.
These
results
underscore
divergence
underlying
changes
highlight
how
distinct
may
neuropsychiatric
disorders
versus
their
treatment.
Annual Review of Medicine,
Journal Year:
2023,
Volume and Issue:
75(1), P. 129 - 143
Published: Sept. 20, 2023
Major
depressive
disorder
(MDD)
is
a
leading
cause
of
suicide
in
the
world.
Monoamine-based
antidepressant
drugs
are
primary
line
treatment
for
this
mental
disorder,
although
delayed
response
and
incomplete
efficacy
some
patients
highlight
need
improved
therapeutic
approaches.
Over
past
two
decades,
ketamine
has
shown
rapid
onset
with
sustained
(up
to
several
days)
effects
whose
MDD
not
responded
conventional
drugs.
Recent
preclinical
studies
have
started
elucidate
underlying
mechanisms
ketamine's
properties.
Herein,
we
describe
compare
recent
clinical
findings
provide
broad
perspective
relevant
action
ketamine.
Proceedings of the National Academy of Sciences,
Journal Year:
2023,
Volume and Issue:
120(49)
Published: Nov. 27, 2023
Ketamine
has
emerged
as
a
transformative
and
mechanistically
novel
pharmacotherapy
for
depression.
Its
rapid
onset
of
action,
efficacy
treatment-resistant
symptoms,
protection
against
relapse
distinguish
it
from
prior
antidepressants.
discovery
reconceptualization
the
neurobiology
depression
and,
in
turn,
insights
elaboration
its
mechanisms
action
inform
studies
pathophysiology
related
disorders.
It
been
25
y
since
we
first
presented
our
ketamine
findings
Thus,
is
timely
this
review
to
consider
what
have
learned
suggest
future
directions
optimization
rapid-acting
antidepressant
treatment.
Pharmaceuticals,
Journal Year:
2025,
Volume and Issue:
18(2), P. 157 - 157
Published: Jan. 24, 2025
Plastogens
are
a
class
of
therapeutics
that
function
by
rapidly
promoting
changes
in
neuroplasticity.
A
notable
example,
ketamine,
is
receiving
great
attention
due
to
its
combined
rapid
and
long-term
antidepressant
effects.
Ketamine
an
N-methyl-D-aspartate
receptor
(NMDAR)
antagonist,
and,
addition
therapeutic
activity,
it
associated
with
psychotomimetic
dissociative
side
Stinels—rapastinel,
apimostinel,
zelquistinel—are
also
plastogens
not
only
effects
but
improved
safety
tolerability
profiles
compared
ketamine.
Previous
descriptions
the
mechanism
which
stinels
modulate
NMDAR
activity
have
been
inconsistent
at
times,
contradictory.
The
purpose
this
review
clarify
action
contextualize
within
broader
NMDAR-targeting
therapeutics.
In
review,
we
present
rationale
behind
targeting
NMDARs
for
treatment-resistant
depression
other
psychiatric
conditions,
describe
various
mechanisms
regulated
different
classes
therapeutics,
evidence
stinel
mechanism.
contrast
previous
glycine-like
partial
agonists,
define
as
positive
allosteric
modulators
novel
regulatory
binding
site.
Psychopharmacology,
Journal Year:
2024,
Volume and Issue:
241(7), P. 1399 - 1415
Published: March 9, 2024
Abstract
Rationale
Ketamine
produces
dissociative,
psychomimetic,
anxiolytic,
antidepressant,
and
anesthetic
effects
in
a
dose
dependent
manner.
It
has
complex
mechanism
of
action
that
involve
alterations
other
glutamate
receptors.
The
metabotropic
receptor
5
(mGluR5)
been
investigated
relation
to
the
psychotic
properties
ketamine,
while
its
role
mediating
therapeutic
ketamine
remains
unknown.
Objectives
We
mGluR5
on
anxiolytic
fear
memory-related
adult
male
Wistar
rats.
Methods
Two
sets
experiments
were
conducted.
first
utilized
positive
allosteric
modulator
CDPPB
investigate
how
acute
activation
regulates
(10
mg/kg).
then
tested
synergistic
antidepressant
effect
antagonism
by
combining
MTEP
with
sub-effective
(1
Behavioral
despair,
locomotor
activity,
anxiety-like
behavior,
memory
respectively
assessed
forced
swim
test
(FST),
open
field
(OFT),
elevated
plus
maze
(EPM),
auditory
conditioning.
Results
Enhancing
activity
via
occluded
without
changing
activity.
Furthermore,
concomitant
administration
exhibited
robust
effect.
+
treatment,
however,
blocked
observed
sole
or
low
ketamine.
Conclusions
These
findings
suggest
suppressed
is
required
for
Consequently,
enhances
effectiveness
but
eliminates
effects.
Proceedings of the National Academy of Sciences,
Journal Year:
2023,
Volume and Issue:
120(49)
Published: Nov. 27, 2023
Individuals
with
a
history
of
early-life
stress
(ELS)
tend
to
have
an
altered
course
depression
and
lower
treatment
response
rates.
Research
suggests
that
ELS
alters
brain
development,
but
the
molecular
changes
in
following
may
mediate
antidepressant
not
been
systematically
studied.
Sex
gender
also
impact
risk
response.
Here,
we
leveraged
existing
RNA
sequencing
datasets
from
1)
blood
samples
depressed
female-
male-identifying
patients
treated
escitalopram
or
desvenlafaxine
assessed
for
failure;
2)
nucleus
accumbens
(NAc)
female
male
mice
exposed
and/or
adult
stress;
3)
NAc
after
stress,
imipramine
ketamine,
failure.
We
find
transcriptomic
signatures
correspond
nonresponse,
across
species
multiple
classes
antidepressants.
Transcriptomic
correspondence
outcome
was
stronger
among
females
weaker
males.
next
pharmacologically
tested
these
predictions
our
mouse
model
social
defeat
either
chronic
acute
ketamine.
Among
mice,
strongest
predictor
behavior
interaction
between
ketamine
treatment.
males,
however,
early
experience
were
poor
predictors
behavior,
mirroring
bioinformatic
predictions.
These
studies
provide
neurobiological
evidence
adaptations
related
sex
contribute
